The connective tissues of humans and non-human animals are constantly subject to stresses and strains from mechanical forces that can result in afflictions, such as arthritis (both rheumatoid and osteoarthritis), joint inflammation and stiffness. This is true for both humans and non-human animals, and particularly as they age. The underlying causes of rheumatoid arthritis and/or osteoarthritis are different such that rheumatoid arthritis is characterized as an autoimmune disease affecting both the joints and systemic immune functions, whereas osteoarthritis results from deterioration of the articular cartilage which may result in local inflammation of the joints. While a greater portion of humans with arthritis have rheumatoid arthritis, most of the arthritis occurring in companion animals is osteoarthritis.
In osteoarthritis or degenerative joint disease, increased stress in the joints results in loss of the integrity of the cartilage matrix and the resulting damage causes the accelerated destruction of cartilage components and synovial fluid. The connective tissues are naturally equipped to repair themselves by manufacturing and remodeling prodigious amounts of collagen (a chief component of connective tissue) and proteoglycans—the other major component of connective tissues. With aging, there is a decreased ability to restore and synthesize normal collagen structures. This results in pain, deformity and limitation of joint motion.
In dogs, osteoarthritis is a disorder of the synovial joints which is characterized by degeneration of the articular cartilage and by formation of new bone at the joint margins. Hardening of the underlying subchondral bone may also be a feature of osteoarthritis and in some cases, a variable degree of synovial inflammation may be present at some time during the progression of the disease.
The treatment of connective tissue afflictions in both humans and non-human animals can be quite problematic. A simple decrease in the stresses to which the connective tissue is subject is often not usually an option. Consequently, treatment is often directed at controlling the symptoms of the afflictions and not their causes, regardless of the stage of the degenerative process. Presently, steroids such as corticosteroids and other anti-inflammatory materials, such as high doses of aspirin are widely used for the treatment of these afflictions in humans. In veterinary medicine, hyaluronic acid and polysulfonated gylcosaminoglycan are used, particularly for equines to reduce connective tissue pain and swelling. While these materials often relieve the pain and swelling associated with maladies arising from connective tissue problems, almost all drugs eventually lose their effectiveness.
Natural products derived from plants and food have frequently been the source of effective drugs, and in recent years there has been an increased interest in the analysis of these natural products, especially where a clinical benefit is claimed. Compounds that have been identified in foods and may be of clinical benefit are the orally administered chondroprotective agents, glucosamine and chondrotin sulphate, which in the body, are normal constituents of articular cartilage. There are studies to suggest that these agents might be effective in humans in the treatment of osteoarthritis. However, there are few reports in the veterinary literature of the clinical efficacy of these oral chondroprotective agents in dogs and other animals.
In the category of natural food products, it has been found that certain marine organisms contain compounds that when fed to animals aid in the treatment of inflammation. One of these marine organisms is Perna canaliculus (New Zealand Green Lipped Mussel) in which its anti-inflammatory activity was first identified in a clinical study on leukemia.
Initial assessment of the anti-inflammatory activity of Perna canaliculus was first attempted using a polyarthritis model in rats. (Cullen et al. 1975.) These studies, however, failed to show the presence of any significant anti-inflammatory activity in the mussel preparation. In contrast, Miller and Ormrod (1980), using a carrageenan-induced paw edema assay (Winter et al. 1962), were able to show that mussel preparations, when administered intraperitoneally, gave a significant reduction to the swelling of a carrageenan-inducted rat paw edema. Subsequently, they fractionated a non-dialysable, water-soluble fraction from the mussel preparation that possessed the anti-inflammatory activity. The aqueous extract showed a dose-dependent anti-inflammatory activity when administered intraperitoneally which could not be detected upon oral administration of the mussel powder. It was suggested that the water-soluble fraction therefore contained an irritant component possessing apparent anti-inflammatory activity.
Rainsford and Whitehouse (1980) also reported that freeze-dried powder preparations of the whole mussel given orally to rats showed some modest anti-inflammatory activity in the carrageenan-induced paw edema assay, and that this material strikingly reduced the gastric ulcerogenicity of several non-steroidal anti-inflammatory drugs in rats and pigs. In another study, Korthauer and Delatorre (1992) found that the oral administration of a glycosaminoglycan extracted from Perna canaliculus to 26 dogs with arthritis at 10 mg/kg daily for eight weeks alleviated the signs of lameness or faulty posture in a high proportionate number of dogs in the study.
Macrides and Kalafatis, the named inventors of WO 96/05164 for an anti-inflammatory preparation, have established that lipid fractions from Perna canaliculus (in contrast to earlier work on aqueous fractions) are a rich source of compounds which in semipurified extracts, have shown a measure of anti-inflammatory activity when tested in appropriate model systems. In WO 96/05164, a purified active fraction isolated from a lipid extract of Perna canaliculus or Mytilus edulis, has an active component that has been shown to have anti-inflammatory properties. From this active component, a substantially pure form of 5,11,14,17-eicosatetraenoic acid (an omega 3 fatty acid) has been isolated and pharmaceutically acceptable esters, amides and salts thereof have been identified. This compound may be a major constituent of the active fraction isolated from the lipid extract of Perna canaliculus. The lipid extract when fed orally has been shown to reduce inflammation in rats. (Whitehouse et al. 1996.)
While the exact mechanism of Perna canaliculus on arthritic symptoms is unknown, it is thought to be partly due to the presence of a unique eicosatetraenoiec acid (ETA) as well as other unique fatty acids that appear to alter the production of inflammatory agents in the body via the lipoxygenase pathway. As previously discussed, the lipid extract of Perna canaliculus contains a high percentage of these fatty acids and the powder form contains small amounts of the same fatty acids as well as other nutrients such as complex proteins, glycosaminoglycans, vitamins, minerals and amino acids, that may act in synergism to regenerate damaged articular cartilage and synovial fluid. In understanding the ideology of the two main types of arthritis, the lipid extract may be more affective in treating animals and/or individuals with rheumatoid arthritis since studies have shown that omega-3 fatty acids can reduce synovial and systematic inflammatory response. (Volker et al. 1996.) As for the powder form, it may be more beneficial in treating individuals with osteoarthritis since it also contains glycosaminoglycans and other nutrients that might potentially help to regenerate articulate cartilage in the joints. These compounds may also help to maintain joint health in animals not yet exhibiting arthritic symptoms.
Based on the apparent effectiveness of a Perna canaliculus extract as an anti-inflammatory agent, it would be beneficial to provide a pet food that includes a quantity of an active extract of Perna canaliculus in an amount that will provide a pet diet for the maintenance of joint health and the alleviation of arthritic symptoms in companion animals such as dogs, cats and horses.